Bardet-Biedl Syndrome (BBS; OMIM 209900) is a rare, autosomal recessive disorder characterized by a multitude of signs, most prominently a progressive retinal dystrophy, post-natal obesity, polydactyly (one or more extra digits), cognitive impairment, and renal dysplasia.
The incidence of BBS varies between populations. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and the Bedouin tribes throughout the Middle East, most likely due to the high rate of consanguinity in these populations. A relatively high frequency of BBS has also been reported in New Foundland.
BBS has been shown to display a remarkable degree of non-allelic genetic heterogeneity. The disorder was first shown to be genetically heterogenous based on mapping studies performed in large inbred Bedouin kindreds from Israel. The large number of traditional consanguineous marriages within these groups make it possible to identify inbred kindreds with multiple affected individuals that are large enough for independent linkage analysis.
The first BBS locus (now referred to as BBS2) was mapped to chromosome 16 using a large inbred Bedouin kindred. Genetic heterogeneity was demonstrated when a second Bedouin BBS kindred did not map to the chromosome 16 locus. Subsequent studies in the second Bedouin kindred revealed linkage to chromosome 3 (BBS3). A third Bedouin kindred showed linkage to chromosome 15 (BBS4).
To date, studies have demonstrated the existence of nine BBS loci (BBS1-9). A locus on chromosome 11 was assigned the designation BBS1 based on the fact that it appears to be the most common known cause of BBS in some populations, mutated in ˜24% of Caucasians but infrequently in other populations. Each of the other eight genes accounts for <5% of the total mutational load. These nine BBS genes explain only 40-50% of the total mutational load. In about half of BBS families, no mutations have been identified, indicating the presence of other, yet unidentified, BBS genes.
Thus there exists a need for identifying new BBS genes and compositions and assays that are useful in the diagnosis and treatment of BBS. The identification of new BBS genes may further provide important insight into biochemical and developmental pathways involved in common complex disorders including obesity and diabetes mellitus.